Did you mean: myeloablative agonists
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Mayo Clinic Proceedings May 2017Monoclonal gammopathies comprise a spectrum of clonal plasma cell disorders that include monoclonal gammopathy of undetermined significance, multiple myeloma, and... (Review)
Review
Monoclonal gammopathies comprise a spectrum of clonal plasma cell disorders that include monoclonal gammopathy of undetermined significance, multiple myeloma, and Waldenström macroglobulinemia. In this review, we outline the epidemiology, etiology, classification, diagnosis, and treatment of monoclonal gammopathy-associated peripheral neuropathy. Monoclonal gammopathy of undetermined significance is relatively common in the general population, with a prevalence of 3% to 4% among individuals older than age 50 years. Therefore, the presence of M protein in a patient with neuropathy does not automatically indicate a causal relationship. Monoclonal gammopathy-associated peripheral neuropathy is often a difficult diagnosis with limited treatment options. Studies addressing the optimal approach to diagnosis and management of this entity are limited. In addition to a review of the literature, we present a diagnostic approach to patients with monoclonal gammopathy-associated peripheral neuropathy and discuss available data and options for treatment.
Topics: Administration, Intravenous; Biomarkers; Demyelinating Autoimmune Diseases, CNS; Diagnosis, Differential; Glycoproteins; Humans; Immunoglobulins; Immunologic Factors; Monoclonal Gammopathy of Undetermined Significance; Myeloablative Agonists; Peripheral Nervous System Diseases; Plasmapheresis; Prognosis; Rituximab; Vidarabine
PubMed: 28473042
DOI: 10.1016/j.mayocp.2017.02.003 -
Blood Jul 2014An essential component of allogeneic and autologous hematopoietic cell transplantation (HCT) is the conditioning regimen administered before the hematopoietic cell... (Review)
Review
An essential component of allogeneic and autologous hematopoietic cell transplantation (HCT) is the conditioning regimen administered before the hematopoietic cell infusion. Early regimens relied on dose intensity, assuming that high-dose chemoradiotherapy would eliminate malignant disease and reinfusion of the graft would then restore hematopoiesis. However, as the contribution of graft-versus-tumor effects to the success of allogeneic HCT was recognized over time, in an effort to exploit these, many investigators lowered the dose of radiation and chemotherapeutic agents in the preparative regimen. This resulted in a major paradigm shift, and consequently, the pool of eligible patients underwent a remarkable expansion. In this article, we provide a review of the definition of high-dose, reduced-intensity, and nonmyeloablative conditioning regimens, the most commonly used agents and combinations, and the evolution of some early regimens. We also provide a brief review of the toxicities associated with these regimens.
Topics: Allografts; Antilymphocyte Serum; Antineoplastic Combined Chemotherapy Protocols; Autografts; Clinical Trials as Topic; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Myeloablative Agonists; Radioimmunotherapy; Transplantation Conditioning; Whole-Body Irradiation
PubMed: 24914142
DOI: 10.1182/blood-2014-02-514778 -
Journal of Clinical Oncology : Official... Mar 2019Single-cycle melphalan 200 mg/m and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free... (Comparative Study)
Comparative Study Randomized Controlled Trial
PURPOSE
Single-cycle melphalan 200 mg/m and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression.
PATIENTS AND METHODS
Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS.
RESULTS
The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms.
CONCLUSION
Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Consolidation Chemotherapy; Dexamethasone; Disease Progression; Female; Hematopoietic Stem Cell Transplantation; Humans; Lenalidomide; Maintenance Chemotherapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Myeloablative Agonists; Progression-Free Survival; Prospective Studies; Remission Induction; Reoperation; Time Factors; Transplantation, Autologous; United States; Young Adult
PubMed: 30653422
DOI: 10.1200/JCO.18.00685 -
Blood Feb 2023
Topics: Mice; Animals; Transplantation, Homologous; Cyclophosphamide; Hematopoietic Stem Cell Transplantation; T-Lymphocytes
PubMed: 36757730
DOI: 10.1182/blood.2022018584 -
Journal of Clinical Oncology : Official... Feb 2022Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies.
PURPOSE
Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).
METHODS
This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS).
RESULTS
Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; = .02), 76.2% (HR, 1.02; 0.60 to 1.72; = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; = .037).
CONCLUSION
CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.
Topics: Adolescent; Adult; Aged; Calcineurin Inhibitors; Chronic Disease; Cyclophosphamide; Disease-Free Survival; Drug Therapy, Combination; Female; Germany; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Myeloablative Agonists; Recurrence; Tacrolimus; Time Factors; Transplantation Conditioning; United States; Young Adult
PubMed: 34855460
DOI: 10.1200/JCO.21.02293 -
The Malaysian Journal of Pathology Dec 2017POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the...
POEMS syndrome is the syndrome of Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein and typical Skin changes. A 65-year-old lady presented with the 2-day-history of inability to walk, 4-month-history of progressive worsening of muscle weakness of both lower limbs and 1-year-history of progressive worsening of bilateral numbness of lower limbs. Nerve conduction study revealed generalized sensorimotor demyelinating polyneuropathy. She was initially treated as chronic inflammatory demyelinating polyradiculoneuropathy with intravenous immunoglobulin (IVIG) and high-dose prednisolone. However, she had no significant neurological improvement despite getting standard therapy. In addition to peripheral neuropathy, the presence of hepatosplenomegaly, skin changes, polycythaemia and thrombocytosis prompted for further investigations. She was diagnosed as POEMS syndrome based on the presence of two mandatory major criteria [polyneuropathy, monoclonal plasma cell proliferative disorder (lambda)], one major criterion (sclerotic bone lesions) and three minor criteria (organomegaly, skin changes and thrombocytosis/polycythaemia). She received treatment with melphalan and prednisolone. She achieved clinical improvement and partial response (haematologic and radiological) after six cycles of therapy. We highlight the awareness of this rare syndrome, for patients presenting with peripheral neuropathy and not responding to its standard therapy, by recognizing other associated clinical manifestations and proceeding further diagnostic work-up.
Topics: Aged; Anti-Inflammatory Agents; Female; Humans; Melphalan; Myeloablative Agonists; POEMS Syndrome; Prednisolone
PubMed: 29279594
DOI: No ID Found -
Blood Feb 2022
Topics: Cyclophosphamide; Prednisone; Rituximab; Vincristine
PubMed: 35201332
DOI: 10.1182/blood.2021013620 -
CMAJ : Canadian Medical Association... May 2018
Topics: Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Axilla; Betamethasone; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Drug Therapy; Erythema; Female; Humans; Intertrigo; Middle Aged; Prednisolone; Treatment Outcome; Zinc Oxide
PubMed: 29759966
DOI: 10.1503/cmaj.180078 -
Cancer Nov 2022
Topics: Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Multiple Myeloma; Taste; Transplantation Conditioning; Transplantation, Autologous
PubMed: 36041229
DOI: 10.1002/cncr.34443 -
Nature Cell Biology Jul 2021Haematopoietic stem cells (HSCs) are normally quiescent, but have evolved mechanisms to respond to stress. Here, we evaluate haematopoietic regeneration induced by...
Haematopoietic stem cells (HSCs) are normally quiescent, but have evolved mechanisms to respond to stress. Here, we evaluate haematopoietic regeneration induced by chemotherapy. We detect robust chromatin reorganization followed by increased transcription of transposable elements (TEs) during early recovery. TE transcripts bind to and activate the innate immune receptor melanoma differentiation-associated protein 5 (MDA5) that generates an inflammatory response that is necessary for HSCs to exit quiescence. HSCs that lack MDA5 exhibit an impaired inflammatory response after chemotherapy and retain their quiescence, with consequent better long-term repopulation capacity. We show that the overexpression of ERV and LINE superfamily TE copies in wild-type HSCs, but not in Mda5 HSCs, results in their cycling. By contrast, after knockdown of LINE1 family copies, HSCs retain their quiescence. Our results show that TE transcripts act as ligands that activate MDA5 during haematopoietic regeneration, thereby enabling HSCs to mount an inflammatory response necessary for their exit from quiescence.
Topics: Animals; Cell Proliferation; Cellular Senescence; Chromatin Assembly and Disassembly; DNA Transposable Elements; Endogenous Retroviruses; Enzyme Activation; HEK293 Cells; Hematopoiesis; Hematopoietic Stem Cells; Humans; Interferon-Induced Helicase, IFIH1; Ligands; Long Interspersed Nucleotide Elements; Mice, Inbred C57BL; Mice, Knockout; Myeloablative Agonists; Signal Transduction; Mice
PubMed: 34253898
DOI: 10.1038/s41556-021-00707-9